Why MRP2 testing matters in DMPK programs

MRP2 (ABCC2) is a hepatic canalicular transporter that, alongside BSEP, mediates biliary excretion of conjugated metabolites and bile constituents.

The vesicle-based assay uses estradiol-17β-glucuronide or DNP-SG as a probe substrate to quantify MRP2-mediated transport into inside-out membrane vesicles, in the presence and absence of test compounds, allowing determination of inhibition potency and IC50 values.

MRP2 inhibition is mechanistically linked to impaired biliary excretion and is assessed alongside BSEP, MRP3 and MRP4 to evaluate compensatory bile acid efflux capacity in DILI risk assessment. Because MRP2 and BSEP share the hepatic canalicular membrane, combined inhibition of both transporters is considered a higher-risk DILI signal than inhibition of either alone.